Antiglycation and Antioxidant Effect of Nitroxyl towards Hemoglobin

Abstract

Donors of nitroxyl and nitroxyl anion (HNO/NO−) are considered to be promising pharmacological treatments with a wide range of applications. Remarkable chemical properties allow nitroxyl to function as a classic antioxidant. We assume that HNO/NO− can level down the non-enzymatic glycation of biomolecules. Since erythrocyte hemoglobin (Hb) is highly susceptible to non-enzymatic glycation, we studied the effect of a nitroxyl donor, Angeli’s salt, on Hb modification with methylglyoxal (MG) and organic peroxide―tert-butyl hydroperoxide (t-BOOH). Nitroxyl dose-dependently decreased the amount of protein carbonyls and advanced glycation end products (AGEs) that were formed in the case of Hb incubation with MG. Likewise, nitroxyl effectively protected Hb against oxidative modification with t-BOOH. It slowed down the destruction of heme, formation of carbonyl derivatives and inter-subunit cross-linking. The protective effect of nitroxyl on Hb in this system is primarily associated with nitrosylation of oxidized Hb and reduction of its ferryl form, which lowers the yield of free radical products. We suppose that the dual (antioxidant and antiglycation) effect of nitroxyl makes its application possible as part of an additional treatment strategy for oxidative and carbonyl stress-associated diseases.

Histidine-Bound Dinitrosyl Iron Complexes: Antioxidant and Antiradical Properties

“…The nitroxyl anion (NO − ) is a product of the single-electron reduction of NO • in living systems, existing in equilibrium with its protonated form, nitroxyl (HNO) [4,79]. NO − /HNO is known to exhibit both pro-oxidant and antioxidant properties [1,4,80].…”

“…The nitroxyl anion (NO − ) is a product of the single-electron reduction of NO • in living systems, existing in equilibrium with its protonated form, nitroxyl (HNO) [4,79]. NO − /HNO is known to exhibit both pro-oxidant and antioxidant properties [1,4,80]. As a result of NO − interacting with molecular oxygen in the following reaction, a strong oxidizer, peroxynitrite (ONOO − ), is supposedly formed [1]:…”

“…Under these conditions, Mb originates from damaged cardiomyocytes. The protonated nitroxyl anion HNO inhibits lipid peroxidation by reducing peroxyl (LOO • ) and alkoxyl (LO • ) radicals [4,65]:…”

“…Physiological derivatives of nitric oxide (NO • ) including dinitrosyl iron complexes (DNICs) perform numerous functions in living systems [1][2][3][4]. DNICs have a wide range of biological activities: they participate in NO • scavenging, have hypotensive, cytoprotective, and antioxidant properties, inhibit platelet aggregation, increase the elasticity of erythrocyte membranes, and promote wound healing [3,[5][6][7][8][9][10].…”

Globin Associated Oxidative Stress

“…In a study of the antioxidant effects of nitroxyl and nitroxyl anion (HNO/NO − ) on Hb, Kosmachevskaya et al show that nitroxyls (from Angeli's salt) can decrease the levels of glycation by non-enzymatic reactions of Hb through nitrosylation of oxidized Hb and by directly reducing the ferryl form of the globin, decreasing radical propagation and products [3]. Methylglyoxal induced formation of protein carbonyls and advanced glycation end products were decreased by nitroxyl in a dose-dependent way.…”